1,4-dimethylpiperazine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-08-14 - 1990-08-28

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The test substance is applied to intact skin, but also to abraded skin. An occlusive dressing is used, instead of a semi-occlusive dressing.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

The test substance is applied to intact skin, but also to abraded skin. An occlusive dressing is used, instead of a semi-occlusive dressing.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1,4-dimethylpiperazine

EC Number:

203-412-0

EC Name:

1,4-dimethylpiperazine

Cas Number:

106-58-1

Molecular formula:

C6H14N2

IUPAC Name:

1,4-dimethylpiperazine

Details on test material:

- Name of test material (as cited in study report): Jeffcat DMP

Specific details on test material used for the study:

- Name of test material (as cited in study report): 6398-17-20
- Lot/batch No. 90-006
- Physical state: clear, pale yellow liquid
- Analytical purity: considered to be the responsibility of the sponsor
- Stability under test conditions: no apparent change in the physical state ot the test article during administration

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hare-Marland, Hewitt, NJ
- Age at study initiation: adult
- Weight at study initiation: 2.480 - 2.662 - 2.154 - 2.167 - 2.902 - 2.960 kg
- Housing: Rabbits were housed individually in cages sized in accordance with the ''Guide for the Care and Use of Laboratory Animals'' of
the Institute of Laboratory Animal Resources, National Research Council.
- Diet (e.g. ad libitum): Purina Lab Rabbit Ration HF, ad libitum
- Water (e.g. ad libitum): fresh tap water, ad libitum. Water is monitored for contaminants at periodic intervals according to Standard Operating Procedure PH-018.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C±3°C (63-73°F)
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h light, 12h dark

Test system

Type of coverage:

occlusive

Preparation of test site:

other: clipped; one site abraded

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml/site, 3 sites per animal

Duration of treatment / exposure:

4h (upper dorsal site) and 24h (lower dorsal sites)

Observation period:

Upper dorsal site: at 30min, 60min, 24h ,48h, 72h, daily from Day 4 to Day 14 after patch removal
Lower dorsal sites: at 24h, 48h and 72h, and daily from Day 4 to Day 14 after application of the test material

Number of animals:

6 (3F and 3M)

Details on study design:

TEST SITE
- Area of exposure: upper dorsal trunk (intact), lower dorsal trunk (1 intact and 1 abraded site), clipped free of fur
- Type of wrap if used: gauze patch, rubber dam and an elastic bandage to retard evaporation

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with water and gauze
- Time after start of exposure: 4h (upper sites) and 24h (lower sites)

SCORING SYSTEM: observation
Draize Evaluation of Dermal Irritation, Primary Dermal Irritation Index and Modified Primary Dermal Irritation Index

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Score:

7.92

Max. score:

8

Remarks on result:

other: severe dermal irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal: 6/6

Time point:

other: 30-60min, 24h, 48h, 72h and daily until Day 14

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

4h and 24h exposure (14 days observation)

Remarks on result:

other: at all sites: severe erythema and necrosis

Results 3

Irritation parameter:

edema score

Basis:

animal: 6/6

Time point:

other: 24h, 48h, 72h and daily until Day 14

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

4h and 24h exposure (14 days observation)

Remarks on result:

other: at all sites: severe edema, necrosis

Results 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 5

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 6

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 7

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 8

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 9

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 10

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 11

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 12

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 13

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 14

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 15

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritant / corrosive response data:

All animals scored 4 (severe erythema and severe edema) which remained present in all animals during whole observation period (up to 14days).

Applicant's summary and conclusion

Interpretation of results:

Category 1C (corrosive) based on GHS criteria

Conclusions:

The test article was considered to be a severe dermal irritant at both 4 and 24 hour exposures. Necrosis of the skin at each application site was observed at the 24, 48 and 72 hour observation periods and on Days 4 through 14. The study was terminated following the Day 14 observation period. (Primary Irritation Index, according to Draize = 7.92, modified Primary Irritation Index = 8.00). Based on these results and according to the criteria laid down in the CLP Regulation, the substance is considered classified as corrosive to the skin category 1C.